The long-range objectives of the proposed research are (1) to contribute to the understanding of the role of the cholera exo-enterotoxin (choleragen) in the causation of the symptomatology of cholera and (2) to develop, experimentally, practical methods of preventing cholera or of interrupting the disease process. To these ends, we propose to continue our previous studies on perorally induced antitoxic immunity to define the mechanism(s) involved; to continue our studies on the interrelationships between choleragen and choleragenoid, the antigenically identical spontaneously formed toxoid, and to attempt to define further their interaction with cellular receptors. In addition we intend to complement and support interrelated studies on the genetics of toxinogenesis in V. cholerae (R. K. Holmes, application pending) by production, purification and characterization of products of interest from "mutant strains" of V. cholerae. It is anticipated that these studies will help lead to a practical and effective means of immunization against cholera and perhaps other infectious diarrheal diseases and that they will provide information bearing on the mode of action of cholera toxin in the causation of the diarrhea of cholera and in the activation of adenyl cyclase in other systems.